Overview
Pharmacodynamics is the study of what a drug does to the body. It examines molecular, biochemical, physiological, and clinical effects. All drugs act by interacting with biological targets: receptors, enzymes, ion channels, transporters, DNA/RNA, and signalling proteins.
It is derived from the terms Pharmakon (drug) and Dynamikos (power)
Pharmacodynamics vs pharmacokinetics
| Pharmacodynamics | Pharmacokinetics |
|---|---|
| What the drug does to the body | What the body does to the drug |
| Drug effects | Drug movement |
| Receptor interactions | ADME |
| Mechanism of action | Drug concentration changes |
Examples of pharmacodynamic effects
| Drug | Pharmacodynamic Effect | Clinical Goal |
|---|---|---|
| Aspirin | Inhibits platelet aggregation | Prevents MI/stroke |
| ACE inhibitors | Vasodilation, ↓ BP | Prevents cardiovascular/renal complications |
| Insulin | Lowers blood glucose | Prevents diabetic complications |
Types of pharmacodynamics actions
| Action | Description | Example |
|---|---|---|
| Stimulation | Salbutamol stimulates β2 receptors → bronchodilation | Adrenaline stimulates adrenergic receptors |
| Depression or inhibition | The drug reduces receptor activity or downstream signaling | Sedatives depress CNS activity |
| Antagonism | Drugs bind receptors but do not activate them. Instead they block endogenous ligands from binding. | Naloxon blocks opioid receptors, and atropine blocks muscarinic receptors |
| Stabilizing action | The drug neither stimulates nor blocks significantly, but stabilizes cellular activity | Some antiarrhythmics stabilize ion channels |
| Direct chemical action | The drug acts chemically rather than through a receptor | Antacids neutralize acid, and chelator bind metals |
Pharmacodynamic interactions
| Interaction | Description | Examples |
|---|---|---|
| Antagonist interaction | The interactions between receptor agonist and antagonists | |
| Additive interactions | The response elicited is equal to the combined response of individual drugs, e.g., blood pressure reduction with ACEi (8 mmHg) and CCBs (20 – 28 mmHg) causes a reduction of about 25 – 36 mmHg. | Blood pressure reduction with ACEi and CCBs |
| Synergistic interactions | The response elicited is greater than the combined response of individual drugs | Bactericidal effect > bacteriostatic effect when combining trimethropim and sulfamethoxazole |
| Potentiation | A drug enhances the effect of another drug, but does not cause it when given alone | Cimetidine enhances the sedative effects of diazepam |
Potency vs efficacy
| Potency | Efficacy | |
|---|---|---|
| Definition | Amount needed for effect | Maximum effect achievable |
| Measurement | Measured by EC50 | Measured by Emax |
Summary table
| Concept | Main Meaning |
|---|---|
| Pharmacodynamics | What a drug does to the body |
| Emax | Maximum possible effect |
| EC50 | Concentration producing 50% effect |
| Potency | Amount needed for effect |
| Efficacy | Maximum achievable effect |
| Kd | Drug-receptor affinity |
| Agonist | Activates receptor |
| Antagonist | Blocks receptor |
| Spare receptors | Max effect before full occupancy |
| Downregulation | Fewer receptors after agonist exposure |
| Upregulation | More receptors after antagonist exposure |
| Therapeutic index | Drug safety margin |
| Tolerance | Reduced response over time |
Maximum effect (Emax)
- This is the maximum effect achievable by a drug: Increasing the dose beyond this does not increase the effect
- High Emax = high efficacy
- Low Emax = low efficacy
- For example:
- Morphine eventually reaches a ceiling of analgesic effect
EC50
- This is the drug concentration producing 50% of the maximal effect
- Lower EC50 → greater potency
- Higher EC50 → lower potency
Hill coefficient
- This measures the steepness of the dose-response curve
- 2 = small dose changes → large effect changes
- 3 = Near “all-or-none” response
- Drugs with steep dose-response curves require careful dosing and have a higher toxicity risk
Therapeutic index
- This measures the drug safety
- TD50 = toxic dose in 50%
- ED50 = effective dose in 50%
- Therapeutic index = TD50/ED50
- A higher therapeutic index = safer drug
- A lower therapeutic drug = a narrow therapeutic window
- Examples of drugs with a narrow therapeutic index include digoxin, lithium, warfarin, and phenytoin
Receptor Regulation
- Downregulation
- Chronic agonist exposure → fewer receptors → tolerance
- Examples of receptors that are downregulated include opioid and insulin receptors
- Upregulation
- Chronic antagonist or agonist exposure → more receptors → enhanced action
- An example is when rebound tachycardia occurs after withdrawing beta-blockers
- Chronic nicotine use also causes receptors to be upregulated, which contributes to addiction
Tolerance
- Tolerance is a reduced response to the same drug dose over time due to:
- Receptor downregulation
- Desensitization
- Altered signaling
- An example is opioid tolerance
- Opioid receptors activate arrestins → reduced G-protein signaling and receptor internalization → reduced analgesic response
- Tachyphylaxis is tolerance that develops rapidly
Dose-Response Relationship
- The dose-response relationship is the degree of effect produced by a drug as a function of the dose (amount) administered
- A dose-response curve shows the relationship between:
- Drug dose/concentration on the x-axis
- Magnitude of response on the y-axis
Definition of terms
| Term | Definition |
|---|---|
| Graded dose response | This measures the effect of a drug in one individual. Increasing the dose increases the response until it reaches a plateau (Emax) |
| Quantal dose response | This measures how a proportion of the population responds to various doses of a drug. It is used to calculate ED50, TD50, and LD50 |
| Efficacy (Emax) | The maximal response produced by a drug, which depends on the number of drug-receptor complexes formed |
| Potency | The dose of a drug that is required to elicit a given response. The lower the dose required to elicit the response, the more potent the drug is |
| Effective dose 50% (ED50) | The dose at which 50% of individuals show the specified quantal effect; a drug with a lower ED50 is more potent than drug with a higher ED50 |
| Median toxic dose (TD50) | The dose at which 50% of people show toxic side-effects |
| Median lethal dose (LD50) | The dose at which 50% of individuals are killed |
| Therapeutic index (TI) | The ratio of the dose that elicits a toxic response in 50% of treated individuals divided by the dose that elicits a therapeutic response in 50% of treated individuals (TI = TD50/ED50) |
| Therapeutic window | This is ****more clinically relevant than therapeutic index. It is the dosage range between the minimum effective therapeutic dose and the minimum toxic dose |
Steep vs flat dose response curves
| Feature | Steep Curve | Flat Curve |
|---|---|---|
| Dose increase effect | Large effect increase | Small effect increase |
| Safety margin | Narrow | Wide |
| Toxicity risk | Higher | Lower |
| Monitoring | Often needed | Less needed |
| Dose individualization | Important | Less important |
| Clinical desirability | Usually undesirable | Usually desirable |